In a normal human being, blood flows from the veins of the body to the right heart chambers. The blood then passes through the lungs (where the red cells pick up oxygen), back to the left heart chambers, and then out of the left heart through the aorta. This sequence of blood flow and the passage through which the blood moves through the body can be studied by ultrasonic imaging, a conventional technique which translates the reflection of sound waves into a visual image. Over the past decade, there has been an interest in cardiology in the development of an ultrasonic contrast agent that is capable of passing through the small vessels of the lungs. An ultrasound contrast agent capable of passing through the small blood vessels of the lungs would allow study of the left side of the heart with conventional medical ultrasound technology, e.g. echocardiography or vascular ultrasound.
One common and clinically useful method of studying the right heart chambers involves the injection of small bubbles, created by shaking or agitating liquid, into the cardiovascular system. These bubbles are generally larger than 10 microns. Although these microbubbles are easily visualized by ultrasound in the right heart chambers, they are filtered out by the capillaries of the lungs and, thus, are not transferred to the left heart chambers. Therefore, they can not and do not enhance ultrasound imaging of the left heart chambers. Two contrast agents are currently under investigation in the United States which also create small microbubbles that are allegedly able to pass through the lungs. However, these microbubbles have been known to pass back into solution under the high pressure of the left heart, and neither agent has been approved by the FDA for general use. See, Shapiro, J. R. et al., "Prospects of Transpulmonary Contrast Echocardiography," The American College of Cardiography, No. 0735-1097 (1989).
Another example of an ultrasound contrast agent is described in PCT International Application No. PCT/US84/00135 by Feinstein. This application discloses a method of ultrasonic imaging which comprises injecting microparticles or sonicated microbubbles into the circulatory system of an animal or human. The microparticles are formed from an amino acid polymer matrix with magnetic particles embedded therein to reflect intense patterns of ultrasonic waves. While such particles may enhance ultrasonic imaging, they are not biodegradable.
Similarly, a paramagnetic contrast agent for nuclear magnetic resonance and ultrasound is disclosed in European patent application, publication nos. 0186947 and 0184899. This agent uses as a carrier, a water-insoluble macro molecular material comprising a polymeric or polymerized carbohydrate or a polymerized sugar alcohol or derivative therof. These disclosures do not disclose an ultrasonic contrast agent that is biodegradable.
One important use of a left heart ultrasonic imaging agent is in the diagnosis of coronary artery disease, the major cause of death in developed countries. The coronary arteries arise from the aorta and feed the heart muscle. When coronary artery disease blocks blood flow to a portion of the heart, that portion of the heart is in danger. Currently, thallium nuclear scintigraphy is the only noninvasive method of evaluating myocardial blood flow. Thallium scintigraphy is expensive, requires a nuclear isotope, and does not give an evaluation of cardiac performance (as an ultrasound image does).
Thus, the need exists for an ultrasound contrast agent that is safe, reliable, biodegradable and that enhances visualization of vascularized organs and typcially the left heart.